The overall aim of this research is to develop and test computational methods for protein docking that will take into consideration some elements of flexibility and side chain motion. The proposed algorithm is based on the program SurfDock co- authored by Dr. Duncan, in which docking is based on surface properties and interactions. The immediate focus is to extend his rigid-body docking program, SurfDock, to enable it to predict the structure of complexes formed by flexible proteins. SurfDock models protein surfaces using spherical harmonic functions. Spherical harmonics have elegant and unique mathematical properties that he can exploit to represent a wide variety of surface properties (e.g., surface geometry, hydrophobicity, electrostatic potential) at different levels of spatial resolution. Long-range collective motion is represented as a combination of low- frequency modes computed by quasi-harmonic or normal mode analysis, and side-chain flexibility by a set of discrete rotamers. Dr. Duncan then computes spherical harmonic representations for these motions. The SurfDock program will use these representations to optimize the intermolecular interactions. This strategy will be tested using protein complexes of known structure. He will perturb the individual subunits, predict the complex of the modified components, and compare these results with the original structure.